内皮素受体拮抗剂CPU0213和钙拮抗剂CPU86017改善异丙肾上腺素诱导的大鼠心衰的作用机制

成于思; 戴德哉; 季 晖; 戴 茵

内皮素受体拮抗剂CPU0213和钙拮抗剂CPU86017改善异丙肾上腺素诱导的大鼠心衰的作用机制

Mechanism of endothelin receptor antagonist CPU0213 and calcium antagonist CPU86017 ameliorated rats′ heart failure induced by isoproterenol

摘要

摘要: 为了验证内皮素受体拮抗剂CPU0213和钙拮抗剂CPU86017改善异丙肾上腺素（isoproterenol，ISO）诱导的大鼠心衰的分子生物学机制，将SD大鼠均分为5组：正常组、ISO组、药物治疗组（3组）。除正常组外，其余4组均皮下给予异丙肾上腺素（ISO,1 mg/kg,10 d），其中3个治疗组于第10，11天分别皮下注射：氨基胍（30 mg/kg）、CPU0213（30 mg/kg）和CPU86017（4 mg/kg）。结果发现，ISO组，内皮素受体A（ET_A）、iNOS、衰老蛋白p66Shc、ε型蛋白激酶C（PKCε）、瘦素受体（OBRb）、NADPH氧化酶p67^phox、瘦素（leptin）mRNA或蛋白表达均上调，药物治疗后对这些异常均有逆转。CPU0213和CPU86017均通过抑制内皮素受体和氧化应激及下调p66Shc和PKCε等相关分子表达，减轻ISO引起的心衰。

Abstract: The purpose of this experiment was to verify whether endothelin receptor antagonist CPU0213 and calcium antagonist CPU86017 improved isoproterenol (ISO)-induced heart failure in rats by inhibiting p66Shc and PKCε .40 SD male rats were randomly divided into 5 groups.Except for the normal group,the other groups were given isoproterenol for 10 d (1mg/kg,sc).Three treatment groups (sc,mg/kg,from day 10-11) included: aminoguanidine group 30 and CPU0213 group 30 and CPU86017 group 4.It was found that mRNA or the protein expressions of endothelin receptor A (ET_A),iNOS,p66Shc,PKCε,OBRb,NADPH oxidase p67^phox and leptin increased in ISO group.After drug treatment ,the above abnormal indicators were mitigated and even reversed.Hence,it suggested that CPU0213 and CPU86017 improved the ISO- induced heart failure by inhibiting the endothelin receptor and oxidative stress and down-regulating the expressions of p66Shc and PKCε.

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